Dabigatran: Difference between revisions

In 2022, an observational metalmeta-analysis study was performed on direct oral anticoagulants for patients with atrial fibrillation. The study found that dabigatran had comparable rates of ischemic stroke or systemic embolism, intracerebral haemorrhage, and all-cause mortality when compared to other anticoagulants like apixaban, edoxaban, and rivaroxaban. Notably, apixaban was associated with a lower risk of gastrointestinal bleeding than dabigatran and the others. This finding was generally steady for patients aged 80 years or older and those with chronic kidney disease.<ref>{{cite journal | vauthors = Lau WC, Torre CO, Man KK, Stewart HM, Seager S, Van Zandt M, Reich C, Li J, Brewster J, Lip GY, Hingorani AD, Wei L, Wong IC | title = Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation : A Multinational Population-Based Cohort Study | journal = Annals of Internal Medicine | volume = 175 | issue = 11 | pages = 1515–1524 | date = November 2022 | pmid = 36315950 | doi = 10.7326/M22-0511 | s2cid = 253238819 }}</ref>

For patients with moderately reduced kidney function, lower dabigatran doses are recommended due to increased drug exposure and bleeding risk.<ref>''Stangier J, Rathgen K, Stähle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clinical pharmacokinetics. 2010 Apr; 49:259-68.''</ref><ref name="Hijazi_2014">{{cite journal | vauthors = Hijazi Z, Hohnloser SH, Oldgren J, Andersson U, Connolly SJ, Eikelboom JW, Ezekowitz MD, Reilly PA, Siegbahn A, Yusuf S, Wallentin L | title = Efficacy and safety of dabigatran compared with warfarin in relation to baseline renal function in patients with atrial fibrillation: a RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) trial analysis | journal = Circulation | volume = 129 | issue = 9 | pages = 961–970 | date = March 2014 | pmid = 24323795 | doi = 10.1161/circulationaha.113.003628 }}</ref><ref>{{cite journal | vauthors = An J, Cheetham TC, Luong T, Lang DT, Lee MS, Reynolds K | title = Effectiveness and safety of Dabigatran 110 mg versus 150 mg for Stroke Prevention in Patients with Atrial Fibrillation at High Bleeding Risk | journal = Clinical Therapeutics | volume = 45 | issue = 7 | pages = e151-e158e151–e158 | date = July 2023 | pmid = 37380555 | doi = 10.1016/j.clinthera.2023.05.007 }}</ref> Alternative anticoagulants should be considered in severe kidney impairment due to insufficient safety and efficacy data.<ref name="Hijazi_2014" />

The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial showed that impairment of liver function caused by dabigatran occurred in the same frequency as warfarin.<ref>{{cite journal | vauthors = Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L | title = Dabigatran versus warfarin in patients with atrial fibrillation | journal = The New England Journal of Medicine | volume = 361 | issue = 12 | pages = 1139–1151 | date = September 2009 | pmid = 19717844 | doi = 10.1056/NEJMoa0905561 | hdl = 11343/221723 | s2cid = 7425216 | hdl-access = free }}</ref>

Dabigatran has a half-life of approximately 12–1412–17 h and exerts a maximum anticoagulation effect within 2–32 hours after ingestion.<ref>{{citationcite journal needed| vauthors = Muñoz-Corcuera M, Ramírez-Martínez-Acitores L, López-Pintor RM, Casañas-Gil E, Hernández-Vallejo G | title = Dabigatran: A new oral anticoagulant. Guidelines to follow in oral surgery procedures. A systematic review of the literature | journal = Medicina Oral, Patologia Oral y Cirugia Bucal | volume = 21 | issue = 6 | pages = e679–e688 | date = November 20192016 | pmid = 27694780 | pmc = 5116109 | doi = 10.4317/medoral.21202 }}</ref> Fatty foods delay the intestinal absorption of dabigatran, although the [[bioavailability]] of the drug is unaffected.<ref name="Pradaxa FDA label" /> Several studies have demonstrated that dabigatran plasma concentrations are reduced when co-administered with proton pump inhibitors, however it is unclear if this reduction is clinically significant.<ref>{{cite journal | vauthors = Stangier J, Eriksson BI, Dahl OE, Ahnfelt L, Nehmiz G, Stähle H, Rathgen K, Svärd R | title = Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement | journal = Journal of Clinical Pharmacology | volume = 45 | issue = 5 | pages = 555–563 | date = May 2005 | pmid = 15831779 | doi = 10.1177/0091270005274550 | s2cid = 26441767 }}</ref><ref>{{cite journal | vauthors = Kuwayama T, Osanai H, Ajioka M, Tokuda K, Ohashi H, Tobe A, Yoshida T, Masutomi T, Kambara T, Inoue Y, Nakashima Y, Asano H, Sakai K | title = Influence of proton pump inhibitors on blood dabigatran concentrations in Japanese patients with non-valvular atrial fibrillation | journal = Journal of Arrhythmia | volume = 33 | issue = 6 | pages = 619–623 | date = December 2017 | pmid = 29255511 | doi = 10.1016/j.joa.2017.07.013 | pmc = 5729000 }}</ref><ref>{{cite journal | vauthors = Bolek T, Samoš M, Stančiaková L, Ivanková J, Škorňová I, Staško J, Galajda P, Kubisz P, Mokáň M | title = The Impact of Proton Pump Inhibition on Dabigatran Levels in Patients With Atrial Fibrillation | journal = American Journal of Therapeutics | volume = 26 | issue = 3 | pages = e308-e313e308–e313 | date = May 2019 | pmid = 28452843 | doi = 10.1097/mjt.0000000000000599 }}</ref> Dabigatran excretion through [[P-glycoprotein]] pumps is slowed in patients taking strong p-glycoprotein pump inhibitors such as [[quinidine]], [[verapamil]], and [[amiodarone]], thus raising plasma levels of dabigatran.<ref name="EMEA2018">[https://www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_en.pdf "Pradaxa Summary of Product Characteristics" (2018)] {{webarchive|url= https://web.archive.org/web/20190705200927/https://www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_en.pdf |date= 5 July 2019 }}. [[European Medicines Agency]].</ref>